Abstract

Background

Ovarian cancer is the ninth most common cancer worldwide and the fifth most frequent cause of cancer-related deaths in women. However, therapeutic options for patients with recurrent diseases are extremely limited. This study aims to identify molecular changes that characterize the three main ovarian cancer subtypes (serous, endometroid and clear cell) and to explore genetically-guided therapeutic strategy for each subtype.

Methods

85 patients with ovarian cancer who were unselected for their family history of malignancies were included in the study. The histological subtypes included serous (n = 36), endometroid (n = 26), and clear cell (n = 23) carcinomas. Formalin-fixed paraffin-embedded samples obtained from the primary tumor of each patient were used for genetic analysis. Mutational status and copy number of 409 cancer related genes were determined using next-generation sequencing.

Results

Non-synonymous mutations and copy number alterations were detected in all tumor samples. TP53 is the most frequently mutated gene in ovarian carcinoma with more frequent occurrence in the serous (80.6%) and endometroid (61.5%) subtypes. In the serous subtype, BRCA1/2 and DNA damage repair pathway was the most commonly altered cellular pathway, occurring in 44% of the patients. Alterations in the PI3K/AKT/mTOR signaling cascade were the most commonly observed genetic aberrations detected in the endometroid and clear cell subtypes. Of which, genetic alterations of the PIK3CA (26.9% in endometroid; 39.1% in clear cell) and PTEN (26.9% in endometroid, but none in clear cell) genes are more frequently detected. Overall, alterations in actionable pathways were detected in more than 80% of tumor samples.

Conclusions

Our results suggest that genetic aberrations should be taken into considerations to support the treatment selection for serous, endometroid and clear cell ovarian carcinoma. In addition, genetic alterations in PTEN could be used to differentiate between the endometroid and the clear cell subtypes.